Abstract Objective To screen out differentially expressed microRNAs (miRNAs) in the plasma of children with methylmalonic acidemia (MMA), to determine the expression of miR-9-1 in plasma and to preliminarily evaluate the significance of miR-9-1 as a biomarker in MMA. Methods Plasma was obtained from 17 MMA children, 10 hyperhomocysteinemia (HHcy) children without MMA (HHcy group), and 10 normal controls. Of 17 MMA children, 12 had HHcy (MMA+HHcy group), and 5 had no HHcy (MMA group). The differentially expressed miRNAs were screened out by miRNA microarray. Differentially expressed miR-9-1 was selected, and plasma miR-9-1 levels were determined by RT-PCR. Urine was collected from MMA patients who received vitamin B12 treatment, and plasma miR-9-1 levels were determined by RT-PCR after treatment. Results The miRNA microarray analysis showed that 26 miRNAs were differentially expressed, among which 16 miRNAs (including miR-9-1) were down-regulated over 2 times, while 10 miRNAs were up-regulated over 2 times. The MMA+HHcy, MMA and HHcy groups had significantly down-regulated miR-9-1 compared with the normal control group (PConclusions Plasma miR-9-1 is significantly down-regulated in MMA patients, but it is significantly up-regulated after vitamin B12 treatment, suggesting that miR-9-1 may act as a biomarker in monitoring the progression of MMA.
About author:: [1] Deodato F, Boenzi S, Santorelli FM, et al. Methylmalonic and propionic aciduria [J].Am J Med Genet C Semin Med Genet, 2006, 142C (2): 104-112.[2] Tu WJ. Methylmalonic acidemia in mainland China [J].Ann Nutr Metab, 2011, 58(4): 281.[3] Wajner M, Coelho JC. Neurological dysfunction in methylmalonic acidaemia is probably related to the inhibitory effect of methylmalonate on brain energy production [J].J Inherit Metab Dis, 1997, 20(6): 761-768.[4] Richard E, Alvarez-Barrientos A, Desviat LR, et al. Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway [J].J Pathol, 2007, 213(4): 453-461.[5] Jin XF, Wu N, Wang L, et al. Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases[J].Cell Mol Neurobiol, 2013, 33(5): 601- 613.[6] Han LS, Ye J, Qiu WJ, et al. Selective screening for inborn errors of metabolism on clinical patients using tandem mass spectrometry in China: a four-year report[J].J Inherit Metab Dis, 2007, 30(4): 507-514.[7] Kim DJ, Linnstaedt S, Palma J, et al. Plasma components affect accuracy of circulating cancer-related microRNA quantitation [J].J Mol Diagn, 2011, 14(1): 71-80.[8] Melo DR, Kowaltowski AJ, Wajner M, et al. Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic academia[J].J Bioenerg Biomembr, 2011, 43(1): 39-46.[9] Fernandes CG, Borges CG, Seminotti B, et al. Experimental evidence that methylmalonic acid provokes oxidative damage and compromises antioxidant defenses in nerve terminal and striatum of young rats[J].Cell Mol Neurobiol, 2011, 31(5): 775-785.[10] Ribeiro LR, Della-Pace ID, de Oliveira Ferreira AP, et al. Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory[J].Immunobiology, 2013, 218(9): 1175-1183.[11] Jones SW, Watkins G, Le Good N, et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13 [J].Osteoarthritis Cartelage, 2009, 17(4): 464-472.[12] Kaneko Y, Wu GS, Saraswathy S, et al. Immunopathologic processes in sympathetic ophthalmia as signified by microRNA profiling [J].Invest Ophthalmol Vis Sci, 2012, 53(7): 4197-4204.[13] Bazzoni F, Rossato M, Fabbri M, et al. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals[J].Proc Natl Acad U S A, 2009, 106(13): 5282-5287.[14] Liu GD, Zhang H, Wang L, et al. Molecular hydrogen regulates the expression of miR-9, miR-21 and miR-199 in LPS-activated retinal microglia cells [J].Int J Ophthalmol, 2013, 6(3): 280-285.[15] Wan HY, Guo LM, Liu T, et al. Regulation of the transcription f a c t o r N F -k a p p a B 1 b y m i c r o R N A -9 i n h u m a n g a s t r i c adenocarcinoma[J].Mol Cancer, 2010, 9: 16.[16] Okada Y, Kato M, Minakami H, et al. Reduced expression of fliceinhibitory protein (FLIP) and NFkappaB is associated with death receptor-induced cell death in human aortic endothelial cells (HAECs)[J].Cytokine, 2001, 15(2): 66-74.
Cite this article:
LI Yan-Fei,PENG Tao,DUAN Ran-Ran et al. A preliminary study of plasma microRNA levels in children with methylmalonic acidemia[J]. CJCP, 2014, 16(6): 629-633.
LI Yan-Fei,PENG Tao,DUAN Ran-Ran et al. A preliminary study of plasma microRNA levels in children with methylmalonic acidemia[J]. CJCP, 2014, 16(6): 629-633.
Deodato F, Boenzi S, Santorelli FM, et al. Methylmalonic and propionic aciduria [J].Am J Med Genet C Semin Med Genet, 2006, 142C (2): 104-112.
[2]
Tu WJ. Methylmalonic acidemia in mainland China [J].Ann Nutr Metab, 2011, 58(4): 281.
[3]
Wajner M, Coelho JC. Neurological dysfunction in methylmalonic acidaemia is probably related to the inhibitory effect of methylmalonate on brain energy production [J].J Inherit Metab Dis, 1997, 20(6): 761-768.
[4]
Richard E, Alvarez-Barrientos A, Desviat LR, et al. Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway [J].J Pathol, 2007, 213(4): 453-461.
[5]
Jin XF, Wu N, Wang L, et al. Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases[J].Cell Mol Neurobiol, 2013, 33(5): 601- 613.
[6]
Han LS, Ye J, Qiu WJ, et al. Selective screening for inborn errors of metabolism on clinical patients using tandem mass spectrometry in China: a four-year report[J].J Inherit Metab Dis, 2007, 30(4): 507-514.
[7]
Kim DJ, Linnstaedt S, Palma J, et al. Plasma components affect accuracy of circulating cancer-related microRNA quantitation [J].J Mol Diagn, 2011, 14(1): 71-80.
[8]
Melo DR, Kowaltowski AJ, Wajner M, et al. Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic academia[J].J Bioenerg Biomembr, 2011, 43(1): 39-46.
[9]
Fernandes CG, Borges CG, Seminotti B, et al. Experimental evidence that methylmalonic acid provokes oxidative damage and compromises antioxidant defenses in nerve terminal and striatum of young rats[J].Cell Mol Neurobiol, 2011, 31(5): 775-785.
[10]
Ribeiro LR, Della-Pace ID, de Oliveira Ferreira AP, et al. Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory[J].Immunobiology, 2013, 218(9): 1175-1183.
[11]
Jones SW, Watkins G, Le Good N, et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13 [J].Osteoarthritis Cartelage, 2009, 17(4): 464-472.
[12]
Kaneko Y, Wu GS, Saraswathy S, et al. Immunopathologic processes in sympathetic ophthalmia as signified by microRNA profiling [J].Invest Ophthalmol Vis Sci, 2012, 53(7): 4197-4204.
[13]
Bazzoni F, Rossato M, Fabbri M, et al. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals[J].Proc Natl Acad U S A, 2009, 106(13): 5282-5287.
[14]
Liu GD, Zhang H, Wang L, et al. Molecular hydrogen regulates the expression of miR-9, miR-21 and miR-199 in LPS-activated retinal microglia cells [J].Int J Ophthalmol, 2013, 6(3): 280-285.
[15]
Wan HY, Guo LM, Liu T, et al. Regulation of the transcription f a c t o r N F -k a p p a B 1 b y m i c r o R N A -9 i n h u m a n g a s t r i c adenocarcinoma[J].Mol Cancer, 2010, 9: 16.
[16]
Okada Y, Kato M, Minakami H, et al. Reduced expression of fliceinhibitory protein (FLIP) and NFkappaB is associated with death receptor-induced cell death in human aortic endothelial cells (HAECs)[J].Cytokine, 2001, 15(2): 66-74.
